A Phase II Trial of RAD001 in Patients With Recurrent Glioblastoma Multiforme
Overview
- Phase
- Phase 2
- Intervention
- Everolimus
- Conditions
- Glioblastoma Multiforme
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 41
- Locations
- 8
- Primary Endpoint
- Surgery Group: Percentage Change From the Baseline in S6 Kinase Levels
- Status
- Terminated
- Last Updated
- 14 years ago
Overview
Brief Summary
This study will define the safety and efficacy of Everolimus (RAD001) administered daily in patients with glioblastoma multiforme (GBM)
Detailed Description
This was a multicenter, open label, randomized study of RAD001 dosed daily in patients with recurrent GBM. The study was conducted with 2 parallel groups of patients. Group 1 was designed to study the biological effects of RAD001 in patients scheduled to undergo salvage surgical resection, and Group 2 was to enroll patients who were not scheduled for surgery. Patients in Group 1 were randomly assigned to one of three pre-surgery treatment groups (0, 5 or 10 mg/day RAD001 for 7 days). All patients in Group 2 were to receive a fixed daily dose of 10 mg/day oral RAD001.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age 18 years of age or older
- •Histologically confirmed Glioblastoma Multiforme (GBM)
- •Radiographic evidence of disease progression
- •Patients must have evaluable contrast enhancing tumor
- •Availability of paraffin blocks or unstained pathology slides for biomarker studies
- •Karnofsky Performance Status of greater than or equal to 60%
Exclusion Criteria
- •Prior treatment with Mammalian target of rapamycin (mTOR) inhibitor
- •History of another malignancy within 3 years
- •Cardiac pacemaker
- •Ferromagnetic metal implants other than those approves as safe for use in Magnetic resonance imaging (MRI) scanners
- •Claustrophobia
- •Unstable systemic diseases
- •Elevated cholesterol or triglycerides
- •Radiation therapy or cytotoxic chemotherapy \<=4 weeks prior to study enrollment. Patient must have recovered from the toxic effects of a prior chemotherapy.
- •Patients must be off all enzyme inducing anticonvulsants for at least 2 week before study enrollment can occur
- •Need for increasing dose of steroids. Patients on a stable or tapering dose of steroids \>=7 days were permitted.
Arms & Interventions
No Surgery (Everolimus 10 mg)
Participants with recurrent Glioblastoma Multiforme (GBM) not scheduled to undergo salvage surgical resection, received a daily oral dose of 10 mg Everolimus (RAD001) until evidence of disease progression or toxicity.
Intervention: Everolimus
Everolimus 10 mg + Surgery
Participants scheduled to undergo salvage surgical resection received a daily oral dose of 10 mg Everolimus for 7 days prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
Intervention: Everolimus
Everolimus 10 mg + Surgery
Participants scheduled to undergo salvage surgical resection received a daily oral dose of 10 mg Everolimus for 7 days prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
Intervention: Surgery
Everolimus 5 mg + Surgery
Participants scheduled to undergo salvage surgical resection received a daily oral dose of 5 mg Everolimus for 7 days prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
Intervention: Everolimus
Everolimus 5 mg + Surgery
Participants scheduled to undergo salvage surgical resection received a daily oral dose of 5 mg Everolimus for 7 days prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
Intervention: Surgery
Everolimus 0 mg + Surgery
Participants scheduled to undergo salvage surgical resection received no treatment with Everolimus prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
Intervention: Everolimus
Everolimus 0 mg + Surgery
Participants scheduled to undergo salvage surgical resection received no treatment with Everolimus prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
Intervention: Surgery
Outcomes
Primary Outcomes
Surgery Group: Percentage Change From the Baseline in S6 Kinase Levels
Time Frame: Baseline and Day 7-9 (during salvage surgery)
In the Surgery Group, the primary efficacy assessment was inhibition of Mammalian target of rapamycin (mTOR) as defined as ≥75% S6 phosphorylation. The occurrence of S6 phosphorylation was determined by phosphor-S6 immunohistochemical staining. Tumor cells from the initial surgical resection and from the salvage resection were used for assessments.
No Surgery Group: Best Overall Tumor Response
Time Frame: First day of treatment to study discontinuation (up to 60 weeks)
The best overall tumor response is reported for participants with 1 previous relapse and participants with ≥2 previous relapses according to the following categories: Complete Response, Partial Response, Stable Disease and Progressive Disease. Gadolinium chelate-enhanced Magnetic Resonance Imaging (MRI) was used for tumor analysis. The objective assessment of tumor response was evaluated at each site by the designated pathologist based on the Neuro-Oncology criteria for Tumor Response for Central Nervous System (CNS) tumors.
Secondary Outcomes
- Surgery Group: Blood and Brain Tissue Levels of Everolimus (RAD001)(Baseline and Day 7-9 (Blood samples were collected one day prior to surgery and tissue samples were collected during surgery.))
- Surgery Group: Progression-free Survival(After surgery (within 96 hours), Weeks 4 and 8 and then every 8 weeks after restarting treatment until study discontinuation (Up to 28 weeks))
- Surgery Group: Biomarkers Phosphatase and Tensin Homolog (PTEN) and Epidermal Growth Factor Receptor (EGFR)(After surgery, week 4, week 8 and every 8 weeks thereafter)
- No Surgery Group: Progression Free Survival(First day of treatment to study discontinuation (up to 60 weeks))
- Surgery Group: Number of Participants With Adverse Events(First day of treatment to study discontinuation (Up to 28 weeks))